TRANSGENIC AND KNOCK OUT MOUSE SHARED RESOURCE Brigid Hogan, Ph.D., Director; Yuan Zhuang, Ph.D., John Norton, D.V.M. Ph.D., Co.Directors ]'he Transgenic and Knock Out Mouse Facility provides services for the production of transgenic mice and mice. The Facility maintains expertise in microinjection of foreign DNA into fertilized mouse embryos, as well as skills necessary for successful gene targeting experiments using pluripotent mouse embryonic stem (ES) cells. Gene targeting experiments, which utilize homologous recombination of specific endogenous genes at site specific locations, can produce a wide variety of mutations, limited only by the creativity and molecular biology skills of the investigator. Gene "knockouts", large deletions, point mutations, conditional mutations, gene exchanges ("knock-ins") and other sophisticated mutations have been carried out by the Facility. Engineered mutations allow investigators to study gene expression and function in the context of the whole organism and during dynamic processes such as embryonic development, puberty, sexual reproduction tissue regeneration and repair, response to environmental factors, learning and aging. In addition, the effec of modifying mutations and genetic background on a disease process can be investigated. In the study of diseases as complex as cancer, genetically engineered mice are essential tools which can provide important and novel insights. The scientific literature is filled with examples of mice that serve as models of human disease. A Comprehensive Cancer Center, which actively conducts scientific research, is best served by a responsive, on site Transgenic Facility that can become a loyal partner in projects initiated by Cancer Center members who seek to understand the complexities of the disease of cancer. The Shared Facility contributes expertise, equipment and other resources to effectively move individual projects forward in a timely manner.